Oestr-5(10)-ene-3,17-dione

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from March to April 2003

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

17 July 1992

Deviations:

yes

Remarks:

- exposure time 24 hrs instead of 4 hrs, 6 animals instead of 3, rats instead of rabbits, few details in test description and reporting

Principles of method if other than guideline:

A combined study on acute dermal toxicity and on local tolerance was used to assess skin irritation/corrosion (comparable to OECD TG 402 and 404). The study design and reporting deviates from the current OECD TG 404, however, the study is considered sufficient for assessment of this endpoint. As described in ATP 96/54/EC ANNEX IV A, PART B: METHODS FOR THE DETERMINATION OF TOXICITY AND OTHER HEALTH EFFECTS, a strategy of testing for irritancy allows the non-performance of a test if an acute toxicity study by the dermal route has been conducted at the limit test dose with the substance (method B.3), and no skin irritation was observed, further testing for skin irritation (method B.4) may be unnecessary.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Oestr-5(10)-ene-3,17-dione

EC Number:

223-564-1

EC Name:

Oestr-5(10)-ene-3,17-dione

Cas Number:

3962-66-1

Molecular formula:

C18H24O2

IUPAC Name:

(3aS,3bR,9bS,11aS)-11a-methyl-1H,2H,3H,3aH,3bH,4H,5H,6H,7H,8H,9H,9bH,10H,11H,11aH-cyclopenta[a]phenanthrene-1,7-dione

Constituent 2

Reference substance name:

5(10)-Estrene-3,17-dione

IUPAC Name:

5(10)-Estrene-3,17-dione

Constituent 3

Reference substance name:

Delta-5-Norandrostendion

IUPAC Name:

Delta-5-Norandrostendion

Test material form:

not specified

Details on test material:

Purity not specified

Test animals

Species:

rat

Strain:

other: Jcl:SD

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CLEA Japan, Inc.
- Age at study initiation: 7 weeks (male), 10-11 weeks (female)
- Weight at study initiation: 257-288 g (male), 264-272 g (female)
- Housing: 1 animal/cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.7-22.8
- Humidity (%): 42-57
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

occlusive

Preparation of test site:

other: shorn

Vehicle:

other: liquid paraffin

Controls:

other: the untreated skin served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 514 - 576 mg/male; 528 - 544 mg/female

VEHICLE
- Amount(s) applied (volume or weight with unit): 1mL
- Lot No. 2Y28

Duration of treatment / exposure:

24 hours

Observation period:

14 days

Number of animals:

3 males and 3 females

Details on study design:

TEST SITE
- Area of exposure: 4 x 9 cm
- % coverage: 10% of body surface
- Type of wrap: gauze pad

REMOVAL OF TEST SUBSTANCE
- Washing: rinsed out with lukewarm water
- Time after start of exposure: 24 hours

Scoring system: according to OECD404

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: #1 to #6

Time point:

24/48/72 h

Score:

0.1

Max. score:

4

Reversibility:

fully reversible

Results 2

Irritation parameter:

edema score

Basis:

animal: #1 to #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

One male and one female revealed very slight reddenings at only 24 hours after removal of the pad (day 3). The mean values of grades across 3 time-points (24, 48 and 72 hours after removal of the pad) and across all 6 animals were 0.1 for reddenings/scab formation and 0 for swelling, and these findings were temporarily observed.

Other effects:

No systemic intolerance reactions were observed.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

A combined study on acute dermal toxicity and on local tolerance was conducted . The study design and reporting deviates from the current OECD TG 404, however, the study was considered sufficient for assessment of skin irritation/corrosion. A single dermal administration of the test substance for 24 hours to male and female rats at a dose of 2000 mg/kg provoked very slight reddenings at only 24 hours after removal of the pad (day 3) which was fully reversible on day 4 (48 hours after removal of the pad) after administration.

Executive summary:

In a primary dermal irritation study similar to OECD TG 404, (young adult) Jcl:SD rats, female and male (3/sex) were dermally exposed to 514-576 mg/male animal or 528-544 mg/female animal of Delta-5-Norandrostendion in liquid paraffin for 24 hours. Animals then were observed for 14 days. Irritation was scored by the method according to the system recommended in OECD Test Guideline 404.

No local irritations were observed. In this study, the test item is not a dermal irritant.